The broad goal of this research program has been elucidation of interactions between retina and retinal pigment epithelium (RPE). Our focus for this 5 year period is to define physiological mechanisms that control the subretinal space (SRS) and evaluate their relevance for clinical disease. This work is directly pertinent to the prevention and management of diseases that involve pathology of the SRS, including rhegmatogenous retinal detachments, serous detachments, inflammatory disease, age-related maculopathy, and others. With better understanding of the normal physiology, medical therapy may be available to prevent the accumulation of subretinal fluid, to strengthen retinal adhesion, and to minimize degenerative change within the SRS. We will use physiological techniques to measure the adhesiveness of the SRS, to create experimental detachments, and to monitor electrophysiologically the function of retina and RPE. Experiments will be designed to show the importance of interphotoreceptor matrix and intraocular pressure gradients in maintaining the SRS. We will also study RPE transport systems which affect subretinal fluid, with particular attention to agents such as acetazolamide and cyclic nucleotides, which may enhance subretinal fluid removal. Finally, we will model several clinical diseases including serous retinopathy, RPE detachments and ischemia of the retina and RPE. These experiments will primarily utilize rabbits, but will extend to higher animals including primates in order to maximize clinical relevance. Some limited human experiments with monitor RPE function electrophysiologically in correlation with disease that involves the SRS.